It has been for a long time an unsolved question of how the ultimate form of benzo(a)pyrene (BP), benzo(a)pyrene diol epoxide (BPDE-I), reaches nuclear DNA in spite of its instability in aqueous solution. By using an exogenous plasmid DNA method to assay the binding activity of BPDE-I to DNA it was found that the microsomal fraction of the cell homogenate has the ability to stabilize BPDE-I in aqueous solution. However, the inability of partially purified P-450 to stabilize BPDE-I indicates the importance of a lipid moiety in protecting BPDE-I from hydrolysis. Translocation of BPDE-I from microsome to nuclei (demonstrated in human cell culture (KD) and rat hepatocytes) indicates that an active carcinogen metabolite can be transferred from its activation site to the target molecules, a possible mechanism of cytoplasmic activation of carcinogen followed by interaction with nuclear DNA. A portion of BPDE-I remained active in cells by a cellular stabilizing mechanism. Thus, secondary BPDE-I DNA adducts were formed upon cell lysis during the isolation of DNA. This introduced experimental artifacts concerning the amount of carcinogen actually bound to DNA and in turn changes the repair rate of the cells.